Impact of Exacerbations on Emphysema Progression in Chronic Obstructive Pulmonary Disease

Tanabe, Naoya; Muro, Shigeo; Hirai, Toyohiro; Oguma, Tsuyoshi; Terada, Kunihiko; Marumo, Satoshi; Kinose, Daisuke; Ogawa, Emiko; Hoshino, Yuma; Mishima, Michiaki

doi:10.1164/rccm.201009-1535oc

Cited by 161 publications

(209 citation statements)

References 46 publications

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“…Similarly, the mean frequency of hospital admission was 0.06, 0.10 and 0.09 for GOLD 2, GOLD 3 and GOLD 4, respectively, in the present study, whereas the mean was 0.11-0.2, 0.25-0.3 and 0.4-0.54 for GOLD 2, GOLD 3 and GOLD 4, respectively, in previous studies [1,4,10,12]. Such a lower frequency of exacerbation was also observed in the subgroup analysis of the Japanese patients participating the UPLIFT study and in another Japanese report [15,16]. The frequency of chronic bronchitis in our cohort was also lower compared to the other studies [12,17].…”

Section: Discussionsupporting

confidence: 80%

Clinical features and determinants of COPD exacerbation in the Hokkaido COPD cohort study

et al. 2013

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Exacerbations are among the major factors that may affect the natural history of chronic obstructive pulmonary disease (COPD). The aim was to investigate the clinical characteristics and determinants of COPD exacerbations in our 5-year observational cohort study which had a very low exacerbation frequency.A total of 279 patients with COPD participated in the Hokkaido COPD cohort study, and 268 subjects who had clinical data for multiple visits were analysed. Exacerbation was defined in multiple ways: the patient's subjective complaint, symptom definition, requiring prescription change, requiring antibiotic treatment, or requiring hospital admission.Exacerbation frequency (events per person per year) was 0.78¡1.16, 0.24¡0.47, 0.20¡0.43, 0.13¡0.28 and 0.06¡0.19 for subjective complaint and symptom, prescription, antibiotic and hospital admission definitions, respectively. Exacerbation events did not significantly affect the annual decline in forced expiratory volume in 1 s. A high St George's Respiratory Questionnaire total score, especially activity score, and a low body mass index were strongly associated with exacerbation-free survival, exacerbation frequency and development of recurrent exacerbations.Despite the low exacerbation frequency in our cohort, impaired health-related quality of life and weight loss were found to be independent risk factors for COPD exacerbations. @ERSpublications Impaired health-related quality of life and weight loss are independent risk factors for COPD exacerbations

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Section: Discussionsupporting

confidence: 80%

Clinical features and determinants of COPD exacerbation in the Hokkaido COPD cohort study

et al. 2013

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“…Tanabe et al (38) reported that changes in the distribution of low-attenuation areas on computerized tomography images of COPD patients were consistent with the coalescence of neighboring low-attenuation areas due to alveolar wall destruction. Since tissue destruction is the primary mechanism that drives airspace enlargement, AECOPD should also contribute to the progression of COPD.…”

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confidence: 90%

Acute mechanical forces cause deterioration in lung structure and function in elastase-induced emphysema

Szabari

Parameswaran

Sato

et al. 2012

American Journal of Physiology-Lung Cellular and Molecular Phys

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. Acute mechanical forces cause deterioration in lung structure and function in elastase-induced emphysema. Am J Physiol Lung Cell Mol Physiol 303: L567-L574, 2012. First published August 1, 2012; doi:10.1152/ajplung.00217.2012The relation between the progression of chronic obstructive pulmonary disease (COPD) and exacerbations is unclear. Currently, no animal model of acute exacerbation of COPD (AECOPD) exists. The objectives of this study were to evaluate the effects of mechanical forces induced by deep inspirations (DIs) on short-term deterioration of lung structure and function to mimic AECOPD. At 2, 7, or 21 days after treatment with elastase, mice were ventilated with or without DIs (35 cmH 2O airway pressure for 3 s, 2 times/min) for 1 h. Functional residual capacity (FRC) was measured with body plethysmography, and respiratory compliance, resistance, and hysteresivity were obtained via forced oscillations. From hematoxylin and eosin-stained sections, equivalent airspace diameters (D), alveolar wall thickness (W t), number of septal ruptures (N sr), and attachment density (Ad) around airways were determined. FRC, compliance, and hysteresivity statistically significantly increased with time, and both increased due to DIs. Interestingly, DIs also had an effect on FRC, compliance, resistance, and hysteresivity in control mice. The development of emphysema statistically significantly increased D and Wt in time, and the DIs caused subtle differences in D. At 21 days, the application of DIs changed the distribution of D, increased Wt and Nsr, and decreased Ad. These results suggest that once a critical remodeling of the parenchyma has been reached, acute mechanical forces lead to irreversible changes in structure and function, mimicking COPD exacerbations. Thus, the acute application of DIs in mice with emphysema may serve as a useful model of AECOPD. AECOPD; mechanical stress; exacerbation; irreversibility CHRONIC OBSTRUCTIVE PULMONARY disease (COPD), including chronic bronchitis and emphysema, is a slowly developing and progressive disease with episodes of acute exacerbation (AE-COPD). According to the latest Global Initiative for Chronic Obstructive Lung Disease (GOLD) Summary (8a), AECOPD is an acute event characterized by a worsening of the patient's respiratory symptoms that is beyond normal day-to-day variations and leads to a change in medication. Most AECOPD is triggered by bacterial (36) or viral (35) infections, by pollutants (33), or by cold temperature (4). Moreover, severe exacerbation-related hospitalization is associated with an increased risk of mortality, even after discharge (8), with a heavy health care burden worldwide.While the frequency of AECOPD was shown to correlate with lung function decline (5, 34), irreversible structural changes behind the functional decline following AECOPD have been identified only recently. Tanabe et al. (38) reported that changes in the distribution of low-attenuation areas on computerized tomography images of COPD patients were consistent with the coalescence...

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“…[26] The clinical impact of exacerbations on various aspects of the disease has been demonstrated in numerous studies. [27] We know that exacerbations produce worsening symptoms, increase morbidity,[28,29] impair quality of life,[30] increase functional impairment,[31] relate to various comorbidities,[32,33] worsen clinical findings reported by patients,[34] and, ultimately, relate to the progression of disease [35] with a major impact on prognosis. [36] In addition, exacerbations have a significant impact on the financial burden of the disease for the health system.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of clinical variables according to follow-up times in COPD: results from ON-SINT cohort

Lόpez-Campos

Fernández-Villar

Represas-Represas

et al. 2017

European Clinical Respiratory Journal

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Background: COPD is a chronic disease traditionally associated with increased symptoms as lung function deteriorates. Follow-up times in previous cohort studies were limited to a few years. Interestingly, newer longer observational studies show a more comprehensive picture on disease progression over time. Therefore, the question on the relevancy of the follow-up time in cohort studies remains open. Methods: The ON-SINT study is an observational, retrospective, nationwide, real-life cohort study, in which patients diagnosed with COPD were recruited between December 2011 and April 2013 by primary care (PC) and secondary care (SC) physicians. Patients were evaluated at the inclusion visit and at the initial visit when the diagnosis of COPD was first established. Distribution of lung function decline over the years was studied comparing those cases with longer follow-up times, with the median of the distribution as the cutoff point. Results: The sample included 1214 patients of which 857 (70.6%) were recruited by PC and 357 (29.4%) by SC physicians. Median follow-up time was 6.26 years. Mean annual change in the complete cohort were –4.5 (222) ml year–1 for FVC and 5.5 (134) ml year–1 for FEV1. We confirm the variable distribution of FEV1 decline and found that longer follow-up periods reduce this variability. Of note, FEV1 decline was different between groups (shorter: 19.7 [180.4] vs longer: –9.7 [46.9]; p = 0.018). Further, our data revealed differences in the clinical presentation according to follow-up times, with special emphasis on dyspnea (OR: 1.035; 95%CI: 1.014–1.056), exacerbations (OR 1.172; 95%CI 1.045–1.315) and CAT scores (OR 1.047; 95%CI 1.019–1.075) being associated with longer follow-up times. Conclusions: This study describes the impact of follow-up periods on lung function variability, and reveals differences in clinical presentation according to follow-up times, with special emphasis on dyspnea, exacerbations and CAT scores.

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Impact of Exacerbations on Emphysema Progression in Chronic Obstructive Pulmonary Disease

Cited by 161 publications

References 46 publications

Clinical features and determinants of COPD exacerbation in the Hokkaido COPD cohort study

Clinical features and determinants of COPD exacerbation in the Hokkaido COPD cohort study

Acute mechanical forces cause deterioration in lung structure and function in elastase-induced emphysema

Evaluation of clinical variables according to follow-up times in COPD: results from ON-SINT cohort

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